Enveloped viral vectors, and notably lentiviral vectors such as those derived from the human immunodeficiency virus-1 (HIV-1) are promising tools within the scope of gene therapy approaches. However, mass production of clinical grades of such vectors remains a challenge at the present time. Several approaches have been proposed for improving their production: optimization of the transfection of the plasmids required for producing the vector in the host cells (e.g., optimization of the transfection agent, of the cell density, of the ratio of plasmids, etc.) or cell culture conditions focused on particular cell metabolism routes (e.g., addition of lipids, cholesterol, chloroquine, sodium butyrate, etc.) (Ansorge et al. 2010; Schweizer and Merten 2010).
The inventors have the idea of extending this field and of optimizing physico-chemical parameters, and were more particularly interested in the pH conditions. The neutrality of the pH of the medium is considered as a critical parameter for cultivating mammal cells. Moreover, a study reported that pseudotyped lentiviruses with envelope glycoproteins of the virus of vesicular stomatitis (VSV-G) are unstable at pH 6 in a phosphate buffer (Higashikawa and Chang 2001). Considering these elements, the person skilled in the art would have considered that the reduction of pH in culture media would have a negative impact on the production of enveloped viruses.